Synthesis of Thiazolium Derivatives as Advanced Glycation End-Products（AGE）Breakers and Anti-inflammatory Agents

• Main Authors: Chen,Hsing-Yu, 陳欣妤
• Other Authors: Wen-Hsin Huang
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/08467855716367469734

碩士 === 國防醫學院 === 藥學研究所 === 94 === Maillard reaction is a complex series of reactions between reducing sugars and amino groups on proteins, which lead to browning, fluorescence, and cross-linking of protein. Advanced glycation end products（AGEs）, formed during later stages of the Maillard reaction, accumulate in long lived tissue proteins, and may contribute to the development of complications in aging, diabetes, rheumatoid arthritis and atherosclerosis. Current developed drugs for AGEs are AGE inhibitors、AGE breakers and antioxidants. ALT-711 is the first drug in a new class of thiazolium therapeutic agents that break established AGE cross-links between proteins. Regarding ALT-711 as the lead compound of AGE breakers in this laboratory, syntheses and modifications based on ALT-711 were performed. We aimed at synthesis of a series of benzothiazole chemicals to develop higher potency and lower toxicity. The selective target compounds were evaluated bioactivities in vitro and vivo. The target compounds were evaluated to reduce inflammation of carrageenan-inducd paw edema in vivo. Among them, compounds 3、7a-7g、9、11、14、16 showed the better anti-inflammatory activity. Especially compound 11 had significant potent than that of leflunomide. Besides, the 15 compounds were subjected to the screening of AGE inhibition activity in vitro, the results are awaited reports.